In this Phase I application we will examine the feasibility of producing high yield porous nanocrystalline silicon (pnc-Si) membranes for protein purification products. Membranes made of this material are a breakthrough technology, 1000x thinner than conventional and other nanoporous membranes, with tunable pore sizes (5-100 nm) and precise distributions. At just tens of nanometers thick, pnc-Si membranes have no internal void spaces, resulting in minimal loss of filtrate and high permeability, making them ideally suited for rapid and precise biomolecule separations. Research of cellular components and proteins has risen to new levels with advances in separation tools such as two-dimensional liquid chromatography and capillary electrophoresis systems. These tools, however, are typically limited to core facilities at major research centers away from the bench top or the daily workspace of the average biomedical scientist. Laboratory separation and sample- prep tools haven't kept pace with advances in major core facilities. This is in part due to the fact that basic membrane technology has not significantly advanced in decades, still suited best to concentration or micron-scale separations. Pnc-Si membranes will enable consumable separation products that bridge the gap between bench top tools and core facility equipment. In this project we will test the feasibility of scalable production of pnc-Si membranes at reproducible pore sizes with adequate burst pressures to be integrated into stackable membrane modules. We will perform protein concentration and purification experiment using pnc-Si membranes in series and benchmark against industry standard centrifugal spin-tubes. Phase II efforts will fabricate stackable modules with precise cut-offs that fractionate and concentration complex protein mixtures in one pass with the goal of offering chromatography features with the speed and simplicity of membrane filtration. PUBLIC HEALTH RELEVANCE: SiMPore's pnc-Si membranes are a breakthrough technology 1000x thinner than conventional and other nanoporous membranes, with permeability more than 100 times greater and controllable tight pore size distributions. These characteristics enable protein separation and purification with the precision of liquid chromatography, but the speed and simplicity of a membrane filter.